Tissue engineering methods using cell transplantation are known, and for example, may involve for instance open joint surgery (e.g., open knee surgery) and, in case of joint surgery, extensive periods of relative disability for the patient to recuperate in order to ensure that optimal results are achieved. Such procedures are costly, and require extensive medical procedures such as rehabilitation and physical therapy.
Methods using scaffold technologies of various forms, where the scaffold (with, or without cells grown in the scaffold) is inserted into the defect, have suffered from difficulties in performing the cell implantation procedure solely guided by arthroscopy.
Arthroscopic Autologous Cell Implantation (called AACI or ACI using minor surgical interventions) is a surgical procedure for treating cartilage or bone defects, whereby a scaffold is inserted into the defect concomitantly with applying cell suspension or cell mixture with precursor fixatives, into said defect using a needle as for instance a “blunt” needle or a catheter. This implantation procedure is visualized and guided by an arthroscope.
WO 2004/110512 discloses an endoscopic method, useful for treating cartilage or bone defects in mammals, involving identifying the position of defect and applying chondrocytes, chondroblasts, osteocytes and osteoblasts cells into cartilage or bone defect. The cells are applied with a solidafiable support material, such as soluble thrombin and fibrinogen or collagen mixtures. It is envisaged that, for surgery in a convex or concave joint, that a porous membrane may be placed at the site of defect, but removed once the fibrin/cell mix are coagulated in place. The method disclosed in WO 2004/110512 allows tissues to be repaired arthroscopically, i.e. without the need of open joint surgery (e.g., open knee surgery).
Scaffolds are porous structures into which cells may be incorporated. They may be made up of biocompatible, bio-degradable materials and are added to tissue to guide the organization, growth and differentiation of cells in the process of forming functional tissue. The materials used can be either of natural or synthetic origin.
WO 2007/028169 relates to a method for tissue engineering by cell implantation that involves the use of a scaffold in situ at the site of a defect, where the therapeutic cells are fixed in place into the scaffold only once the scaffold is inserted at the site of the tissue defect.
WO 2007/101443 provides preferred scaffold materials for use in the methods and kit of parts of the present invention.
Microparticles have been used as injectable scaffolds for tissue augmentation and support.
WO96/02209 reports on an injectable, biocompatible smooth surfaced carbon coated metallic particles (100-1000 microns in size) for use in combination with a lubricate fluid or gel for augmentation of the urinary sphincter muscle.
Xu and Reid et al. (Annals New York Academy of Sciences Vol. 944:144-159, 2001)) disclose the use of porous biocompatible and biodegradable (PLGA) microcarriers beads (spheres) of diameter 20-40 microns and 100-300 microns to attach hepatoma cells for the formation of three-dimensional cell-degradable microcarrier colonies in culture.
Kang et al. (J. Biomater. Sci. Polymer Edn, Vol 17, No 8, pp 925-939 (2006) discloses the manufacture and use of PLGA microspheres as injectable carriers for cartilage regeneration in rabbit knees. The beads were filtered into a range of 30-80 micron beads. The smaller beads were discarded as they were considered they may migrate to distant organs after implantation.
The present invention provides new and improved compositions for augmentation and regeneration of living tissue in a subject.